Kah Whye Peng

Equity Interest - Non-publicly traded entity ( e.g., stock, stock option, or other ownership interest)

Phase I trial of intravenous vesicular stomatitis virus for treatment of metastatic endometrial cancer

This project is designed to test a new systemic virus therapy for metastatic endometrial cancer. Endometrial cancer is the most common gynecologic cancer in the United States. Advanced stage and recurrent disease are highly lethal and new treatments are desperately needed. Virus therapy has been tested in human clinical trials in several cancers, including gynecologic cancers. We have previously shown that the Vesicular Stomatitis Virus (VSV) potently and rapidly kills endometrial cancer cells and tumors in laboratory experiments. VSV is a non-human virus that normally infects livestock; natural infections in humans are non-lethal, with mild or no symptoms. Prior exposure or infection is rare in the United States and mostly occurs in humans with close contact with livestock (farmers, veterinarians). We have engineered a strain of VSV that carries two human genes with it when it infects cells. The virus this project will study is VSV-hIFN?-NIS. The human interferon beta gene (hIFN?) codes for interferon (IFN) which protects normal cells from VSV effects, and the sodium iodide symporter (NIS) enables tumor cells infected with the virus to concentrate various iodine isotopes which can allow for imaging of tumors infected with the virus. This project includes: 1) a phase I clinical trial of intravenous VSV-hIFN?-NIS in humans with metastatic endometrial cancer in which we will assess safety and toxicity of the virus, determine the maximum tolerated dose of the virus in humans, determine whether tumors infected with the virus are able to be detected with imaging, and early assessment of the impact of the virus on cancer response; 2) studies on the patients enrolled in the trial that will determine the tumor gene signature, virus infectivity and its ability to replicate in tumor, and elimination from the human body; and 3) the impact of the virus on patients' immune responses to the virus and to proteins on endometrial cancer cells. This project will determine the safety profile of VSV-hIFN?-NIS when administered to human subjects and guide us in developing novel treatment(s) for metastatic endometrial cancer.